Microelectrodes in an ophthalmic electrochemical sensor

ABSTRACT

An eye-mountable device includes an electrochemical sensor embedded in a polymeric material configured for mounting to a surface of an eye. The electrochemical sensor includes a working electrode, a reference electrode, and a reagent that selectively reacts with an analyte to generate a sensor measurement related to a concentration of the analyte in a fluid to which the eye-mountable device is exposed. The working electrode can have at least one dimension less than 25 micrometers. The reference electrode can have an area at least five times greater than an area of the working electrode. A portion of the polymeric material can surround the working electrode and the reference electrode such that an electrical current conveyed between the working electrode and the reference electrode is passed through the at least partially surrounding portion of the transparent polymeric material.

CROSS REFERENCE TO RELATED APPLICATIONS

The present application is a continuation of U.S. patent applicationSer. No. 13/650,418, filed Oct. 12, 2012, which is currently pending.The entire disclosure contents of this application are herewithincorporated by reference into the present application.

BACKGROUND

Unless otherwise indicated herein, the materials described in thissection are not prior art to the claims in this application and are notadmitted to be prior art by inclusion in this section.

An electrochemical amperometric sensor measures a concentration of ananalyte by measuring a current generated through electrochemicaloxidation or reduction reactions of the analyte at a working electrodeof the sensor. A reduction reaction occurs when electrons aretransferred from the electrode to the analyte, whereas an oxidationreaction occurs when electrons are transferred from the analyte to theelectrode. The direction of the electron transfer is dependent upon theelectrical potentials applied to the working electrode by apotentiostat. A counter electrode and/or reference electrode is used tocomplete a circuit with the working electrode and allow the generatedcurrent to flow. When the working electrode is appropriately biased, theoutput current is proportional to the reaction rate, which provides ameasure of the concentration of the analyte surrounding the workingelectrode.

In some examples, a reagent is localized proximate the working electrodeto selectively react with a desired analyte. For example, glucoseoxidase can be fixed near the working electrode to react with glucoseand release hydrogen peroxide, which is then electrochemically detectedby the working electrode to indicate the presence of glucose. Otherenzymes and/or reagents can be used to detect other analytes.

SUMMARY

Some embodiments of the present disclosure provide an eye-mountabledevice including a transparent polymeric material, a substrate, anantenna, a two-electrode electrochemical sensor, and a controller. Thetransparent polymeric material can have a concave surface and a convexsurface. The concave surface can be configured to be removably mountedover a corneal surface and the convex surface can be configured to becompatible with eyelid motion when the concave surface is so mounted.The substrate can be at least partially embedded within the polymericmaterial. The antenna can be disposed on the substrate. Thetwo-electrode electrochemical sensor can be disposed on the substrate.The two-electrode electrochemical sensor can include a working electrodehaving at least one dimension less than 25 micrometers, and a referenceelectrode having an area at least five times greater than an area of theworking electrode. The controller can be electrically connected to theelectrochemical sensor and the antenna. The controller can be configuredto: (i) apply a voltage between the working electrode and the referenceelectrode sufficient to generate an amperometric current related to theconcentration of an analyte in a fluid to which the eye-mountable deviceis exposed; (ii) measure the amperometric current; and (iii) use theantenna to indicate the measured amperometric current. A portion of thetransparent polymeric material can surround the working electrode andthe reference electrode such that an electrical current conveyed betweenthe working electrode and the reference electrode is passed through theat least partially surrounding portion of the transparent polymericmaterial.

Some embodiments of the present disclosure provide a system including aneye-mountable device and a reader. The eye-mountable device can includea transparent polymeric material, a substrate, an antenna, atwo-electrode electrochemical sensor, and a controller. The transparentpolymeric material can have a concave surface and a convex surface. Theconcave surface can be configured to be removably mounted over a cornealsurface and the convex surface can be configured to be compatible witheyelid motion when the concave surface is so mounted. The substrate canbe at least partially embedded within the polymeric material. Theantenna can be disposed on the substrate. The two-electrodeelectrochemical sensor can be disposed on the substrate. Thetwo-electrode electrochemical sensor can include a working electrodehaving at least one dimension less than 25 micrometers, and a referenceelectrode having an area at least five times greater than an area of theworking electrode. The controller can be electrically connected to theelectrochemical sensor and the antenna. The controller can be configuredto: (i) apply a voltage between the working electrode and the referenceelectrode sufficient to generate an amperometric current related to theconcentration of an analyte in a fluid to which the eye-mountable deviceis exposed; (ii) measure the amperometric current; and (iii) use theantenna to indicate the measured amperometric current. A portion of thetransparent polymeric material can surround the working electrode andthe reference electrode such that an electrical current conveyed betweenthe working electrode and the reference electrode is passed through theat least partially surrounding portion of the transparent polymericmaterial. The reader can include one or more antennae and a processingsystem. The one or more antennae can be configured to: transmit radiofrequency radiation to power the eye-mountable device, and receiveindications of the measured amperometric current via backscatterradiation received at the one or more antennae. The processing systemcan be configured to determine a tear film analyte concentration valuebased on the backscatter radiation.

Some embodiments of the present disclosure provide a method includingapplying a voltage between a working electrode and a referenceelectrode, measuring an amperometric current through the workingelectrode, and wirelessly indicating the measured amperometric current.The voltage applied between a working electrode and a referenceelectrode can be sufficient to cause electrochemical reactions at theworking electrode. The working electrode and the reference electrode canbe embedded within an eye-mountable device having a concave surface anda convex surface. The concave surface can be configured to be removablymounted over a corneal surface and the convex surface can be configuredto be compatible with eyelid motion when the concave surface is somounted. The working electrode can have at least one dimension less than25 micrometers and the reference electrode can have an area at leastfive times greater than an area of the working electrode. The workingelectrode and the reference electrode can be arranged in theeye-mountable device such that the electrochemical reactions are relatedto a concentration of an analyte in a fluid to which the eye-mountabledevice is exposed. The amperometric current can be measured through theworking electrode while the voltage is applied between the electrodes.The eye-mountable device can include a polymeric material with a portionthat at least partially surrounds the working electrode and thereference electrode such that an electrical current conveyed between theworking electrode and the reference electrode is passed through the atleast partially surrounding portion. The method can include wirelesslyindicating the measured amperometric current via an antenna embeddedwithin the eye-mountable device.

These as well as other aspects, advantages, and alternatives, willbecome apparent to those of ordinary skill in the art by reading thefollowing detailed description, with reference where appropriate to theaccompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a block diagram of an example system that includes aneye-mountable device in wireless communication with an external reader.

FIG. 2A is a bottom view of an example eye-mountable device.

FIG. 2B is an aspect view of the example eye-mountable device shown inFIG. 2A.

FIG. 2C is a side cross-section view of the example eye-mountable deviceshown in FIGS. 2A and 2B while mounted to a corneal surface of an eye.

FIG. 2D is a side cross-section view enhanced to show the tear filmlayers surrounding the surfaces of the example eye-mountable device whenmounted as shown in FIG. 2C.

FIG. 3 is a functional block diagram of an example system forelectrochemically measuring a tear film analyte concentration.

FIG. 4A is a flowchart of an example process for operating anelectrochemical sensor in an eye-mountable device to measure a tear filmanalyte concentration.

FIG. 4B is a flowchart of an example process for operating an externalreader to interrogate an electrochemical sensor in an eye-mountabledevice to measure a tear film analyte concentration.

FIG. 5A shows an example configuration in which an electrochemicalsensor detects an analyte that diffuses from a tear film through apolymeric material.

FIG. 5B shows an example configuration in which an electrochemicalsensor detects an analyte in a tear film that contacts the sensor via achannel in a polymeric material.

FIG. 5C shows an example configuration in which an electrochemicalsensor detects an analyte that diffuses from a tear film through athinned region of a polymeric material.

FIG. 5D shows another example configuration in which an electrochemicalsensor detects an analyte that diffuses from a tear film layer through apolymeric material.

FIG. 5E shows another example configuration in which an electrochemicalsensor detects an analyte a tear film layer that contacts the sensor viaa channel in a polymeric material.

FIG. 5F shows another example configuration in which an electrochemicalsensor detects an analyte that diffuses from a tear film layer through athinned region of a polymeric material.

FIG. 6A illustrates one example arrangement for electrodes in anelectrochemical sensor.

FIG. 6B illustrates another example arrangement for electrodes in anelectrochemical sensor.

FIG. 7A illustrates an example coplanar arrangement for electrodes in anelectrochemical sensor.

FIG. 7B illustrates an example non-coplanar arrangement for electrodesin an electrochemical sensor.

DETAILED DESCRIPTION

In the following detailed description, reference is made to theaccompanying figures, which form a part hereof. In the figures, similarsymbols typically identify similar components, unless context dictatesotherwise. The illustrative embodiments described in the detaileddescription, figures, and claims are not meant to be limiting. Otherembodiments may be utilized, and other changes may be made, withoutdeparting from the scope of the subject matter presented herein. It willbe readily understood that the aspects of the present disclosure, asgenerally described herein, and illustrated in the figures, can bearranged, substituted, combined, separated, and designed in a widevariety of different configurations, all of which are explicitlycontemplated herein.

I. Overview

An ophthalmic sensing platform can include a sensor, control electronicsand an antenna all situated on a substrate embedded in a polymericmaterial formed to be contact mounted to an eye. The control electronicscan operate the sensor to perform readings and can operate the antennato wirelessly communicate the readings from the sensor to an externalreader via the antenna.

The polymeric material can be in the form of a round lens with a concavecurvature configured to mount to a corneal surface of an eye. Thesubstrate can be embedded near the periphery of the polymeric materialto avoid interference with incident light received closer to the centralregion of the cornea. The sensor can be arranged on the substrate toface inward, toward the corneal surface so as to generate clinicallyrelevant readings from near the surface of the cornea and/or from tearfluid interposed between the contact lens and the corneal surface. Insome examples, the sensor is entirely embedded within the contact lensmaterial. For example, the sensor can be suspended in the lens materialand situated such that the working electrode is less than 10 micrometersfrom the polymeric surface configured to mount to the cornea. The sensorcan generate an output signal indicative of a concentration of ananalyte that diffuses through the lens material to the embedded sensor.

The ophthalmic sensing platform can be powered via radiated energyharvested at the sensing platform. Power can be provided by lightenergizing photovoltaic cells included on the sensing platform.Additionally or alternatively, power can be provided by radio frequencyenergy harvested from the antenna. A rectifier and/or regulator can beincorporated with the control electronics to generate a stable DCvoltage to power the sensing platform from the harvested energy. Theantenna can be arranged as a loop of conductive material with leadsconnected to the control electronics. In some embodiments, such a loopantenna can wirelessly also communicate the sensor readings to anexternal reader by modifying the impedance of the loop antenna so as tomodify backscatter radiation from the antenna.

Human tear fluid contains a variety of inorganic electrolytes (e.g.,Ca²⁺, Mg²⁺, Cl⁻), organic solutes (e.g., glucose, lactate, etc.),proteins, and lipids. A contact lens with one or more sensors that canmeasure one or more of these components provides a convenientnon-invasive platform to diagnose or monitor health related problems. Anexample is a glucose sensing contact lens that can potentially be usedfor diabetic patients to monitor and control their blood glucose level.

An example electrochemical sensor is mounted to a sensing platformembedded in a contact lens and includes a working electrode and acounter/reference electrode (i.e., a counter electrode that can alsoserve as a reference electrode). The working electrode can have at leastone dimension less than 25 micrometers. In some examples, the workingelectrode has at least one dimension of about 10 micrometers. Thecounter/reference electrode can have an area at least five times largerthan the working electrode. The electrodes can be situated in a varietyof geometries, including co-planar parallel bars, concentric rings,co-axial discs, etc. The working electrode and the combinationreference-counter electrode can be formed of platinum, palladium,carbon, silver, gold, other suitable conductive materials, and/orcombinations of these, etc. A potentiostat can be connected to the twoelectrodes to apply a potential to the working electrode with respect tothe counter/reference electrode while measuring the current through theworking electrode. More particularly, the potential applied to theworking electrode can be sufficient to generate oxidation and/orreduction reactions of target analytes, in which case the measuredcurrent provides an indication of analyte concentration. The controlelectronics operate the antenna to wirelessly communicate indications ofthe current to the external reader.

Employing a microelectrode, such as a working electrode with a dimensionof approximately 10 micrometers, results in currents in typical signalcurrents of a few nanoamps. At such low currents, and with suchelectrode dimensions, the diffusion of analyte molecules to theelectrode is sufficiently efficient that the amperometric currentsreadily reach the steady state as a result of the sustainablereplenishment of analyte molecules to the working electrode throughdiffusion.

Moreover, low currents allow the sensor to be less sensitive to thevoltage loss due to resistance of the electrolyte material between theelectrodes. That is, sensors with low operating currents generate lessvoltage loss between their electrodes as a result of their sensorcurrent, even when the material between the electrodes has a relativelyhigh resistance. Thus, where the electrodes are embedded in thepolymeric material of the lens, which has a relatively high resistancecompared to a typical aqueous solution employed as an electrolyte, theoperation of the electrochemical sensor can be enhanced by configuringthe working electrode as a microelectrode (e.g., with a dimension lessthan 25 micrometers, about 10 micrometers, or even less than 10micrometers).

II. Example Ophthalmic Electronics Platform

FIG. 1 is a block diagram of a system 100 that includes an eye-mountabledevice 110 in wireless communication with an external reader 180. Theexposed regions of the eye-mountable device 110 are made of a polymericmaterial 120 formed to be contact-mounted to a corneal surface of aneye. A substrate 130 is embedded in the polymeric material 120 toprovide a mounting surface for a power supply 140, a controller 150,bio-interactive electronics 160, and a communication antenna 170. Thebio-interactive electronics 160 are operated by the controller 150. Thepower supply 140 supplies operating voltages to the controller 150and/or the bio-interactive electronics 160. The antenna 170 is operatedby the controller 150 to communicate information to and/or from theeye-mountable device 110. The antenna 170, the controller 150, the powersupply 140, and the bio-interactive electronics 160 can all be situatedon the embedded substrate 130. Because the eye-mountable device 110includes electronics and is configured to be contact-mounted to an eye,it is also referred to herein as an ophthalmic electronics platform.

To facilitate contact-mounting, the polymeric material 120 can have aconcave surface configured to adhere (“mount”) to a moistened cornealsurface (e.g., by capillary forces with a tear film coating the cornealsurface). Additionally or alternatively, the eye-mountable device 110can be adhered by a vacuum force between the corneal surface and thepolymeric material due to the concave curvature. While mounted with theconcave surface against the eye, the outward-facing surface of thepolymeric material 120 can have a convex curvature that is formed to notinterfere with eye-lid motion while the eye-mountable device 110 ismounted to the eye. For example, the polymeric material 120 can be asubstantially transparent curved polymeric disk shaped similarly to acontact lens.

The polymeric material 120 can include one or more biocompatiblematerials, such as those employed for use in contact lenses or otherophthalmic applications involving direct contact with the cornealsurface. The polymeric material 120 can optionally be formed in partfrom such biocompatible materials or can include an outer coating withsuch biocompatible materials. The polymeric material 120 can includematerials configured to moisturize the corneal surface, such ashydrogels and the like. In some instances, the polymeric material 120can be a deformable (“non-rigid”) material to enhance wearer comfort. Insome instances, the polymeric material 120 can be shaped to provide apredetermined, vision-correcting optical power, such as can be providedby a contact lens.

The substrate 130 includes one or more surfaces suitable for mountingthe bio-interactive electronics 160, the controller 150, the powersupply 140, and the antenna 170. The substrate 130 can be employed bothas a mounting platform for chip-based circuitry (e.g., by flip-chipmounting) and/or as a platform for patterning conductive materials(e.g., gold, platinum, palladium, titanium, copper, aluminum, silver,metals, other conductive materials, combinations of these, etc. tocreate electrodes, interconnects, antennae, etc. In some embodiments,substantially transparent conductive materials (e.g., indium tin oxide)can be patterned on the substrate 130 to form circuitry, electrodes,etc. For example, the antenna 170 can be formed by depositing a patternof gold or another conductive material on the substrate 130. Similarly,interconnects 151, 157 between the controller 150 and thebio-interactive electronics 160, and between the controller 150 and theantenna 170, respectively, can be formed by depositing suitable patternsof conductive materials on the substrate 130. A combination of resists,masks, and deposition techniques can be employed to pattern materials onthe substrate 130. The substrate 130 can be a relatively rigid material,such as polyethylene terephthalate (“PET”) or another materialsufficient to structurally support the circuitry and/or electronicswithin the polymeric material 120. The eye-mountable device 110 canalternatively be arranged with a group of unconnected substrates ratherthan a single substrate. For example, the controller 150 and abio-sensor or other bio-interactive electronic component can be mountedto one substrate, while the antenna 170 is mounted to another substrateand the two can be electrically connected via the interconnects 157.

In some embodiments, the bio-interactive electronics 160 (and thesubstrate 130) can be positioned away from the center of theeye-mountable device 110 and thereby avoid interference with lighttransmission to the eye through the center of the eye-mountable device110. For example, where the eye-mountable device 110 is shaped as aconcave-curved disk, the substrate 130 can be embedded around theperiphery (e.g., near the outer circumference) of the disk. In someembodiments, the bio-interactive electronics 160 (and the substrate 130)can be positioned in the center region of the eye-mountable device 110.The bio-interactive electronics 160 and/or substrate 130 can besubstantially transparent to incoming visible light to mitigateinterference with light transmission to the eye. Moreover, in someembodiments, the bio-interactive electronics 160 can include a pixelarray 164 that emits and/or transmits light to be perceived by the eyeaccording to display instructions. Thus, the bio-interactive electronics160 can optionally be positioned in the center of the eye-mountabledevice so as to generate perceivable visual cues to a wearer of theeye-mountable device 110, such as by displaying information via thepixel array 164.

The substrate 130 can be shaped as a flattened ring with a radial widthdimension sufficient to provide a mounting platform for the embeddedelectronics components. The substrate 130 can have a thicknesssufficiently small to allow the substrate 130 to be embedded in thepolymeric material 120 without influencing the profile of theeye-mountable device 110. The substrate 130 can have a thicknesssufficiently large to provide structural stability suitable forsupporting the electronics mounted thereon. For example, the substrate130 can be shaped as a ring with a diameter of about 10 millimeters, aradial width of about 1 millimeter (e.g., an outer radius 1 millimeterlarger than an inner radius), and a thickness of about 50 micrometers.The substrate 130 can optionally be aligned with the curvature of theeye-mounting surface of the eye-mountable device 110 (e.g., convexsurface). For example, the substrate 130 can be shaped along the surfaceof an imaginary cone between two circular segments that define an innerradius and an outer radius. In such an example, the surface of thesubstrate 130 along the surface of the imaginary cone defines aninclined surface that is approximately aligned with the curvature of theeye mounting surface at that radius.

The power supply 140 is configured to harvest ambient energy to powerthe controller 150 and bio-interactive electronics 160. For example, aradio-frequency energy-harvesting antenna 142 can capture energy fromincident radio radiation. Additionally or alternatively, solar cell(s)144 (“photovoltaic cells”) can capture energy from incoming ultraviolet,visible, and/or infrared radiation. Furthermore, an inertial powerscavenging system can be included to capture energy from ambientvibrations. The energy harvesting antenna 142 can optionally be adual-purpose antenna that is also used to communicate information to theexternal reader 180. That is, the functions of the communication antenna170 and the energy harvesting antenna 142 can be accomplished with thesame physical antenna.

A rectifier/regulator 146 can be used to condition the captured energyto a stable DC supply voltage 141 that is supplied to the controller150. For example, the energy harvesting antenna 142 can receive incidentradio frequency radiation. Varying electrical signals on the leads ofthe antenna 142 are output to the rectifier/regulator 146. Therectifier/regulator 146 rectifies the varying electrical signals to a DCvoltage and regulates the rectified DC voltage to a level suitable foroperating the controller 150. Additionally or alternatively, outputvoltage from the solar cell(s) 144 can be regulated to a level suitablefor operating the controller 150. The rectifier/regulator 146 caninclude one or more energy storage devices to mitigate high frequencyvariations in the ambient energy gathering antenna 142 and/or solarcell(s) 144. For example, one or more energy storage devices (e.g., acapacitor, an inductor, etc.) can be connected to the output of therectifier 146 and configured to function as a low-pass filter.

The controller 150 is turned on when the DC supply voltage 141 isprovided to the controller 150, and the logic in the controller 150operates the bio-interactive electronics 160 and the antenna 170. Thecontroller 150 can include logic circuitry configured to operate thebio-interactive electronics 160 so as to interact with a biologicalenvironment of the eye-mountable device 110. The interaction couldinvolve the use of one or more components, such as analyte bio-sensor162, in bio-interactive electronics 160 to obtain input from thebiological environment. Additionally or alternatively, the interactioncould involve the use of one or more components, such as pixel array164, to provide an output to the biological environment.

In one example, the controller 150 includes a sensor interface module152 that is configured to operate analyte bio-sensor 162. The analytebio-sensor 162 can be, for example, an amperometric electrochemicalsensor that includes a working electrode and a reference electrode. Avoltage can be applied between the working and reference electrodes tocause an analyte to undergo an electrochemical reaction (e.g., areduction and/or oxidation reaction) at the working electrode. Theelectrochemical reaction can generate an amperometric current that canbe measured through the working electrode. The amperometric current canbe dependent on the analyte concentration. Thus, the amount of theamperometric current that is measured through the working electrode canprovide an indication of analyte concentration. In some embodiments, thesensor interface module 152 can be a potentiostat configured to apply avoltage difference between working and reference electrodes whilemeasuring a current through the working electrode.

In some instances, a reagent can also be included to sensitize theelectrochemical sensor to one or more desired analytes. For example, alayer of glucose oxidase (“GOD”) proximal to the working electrode cancatalyze glucose oxidation to generate hydrogen peroxide (H₂O₂). Thehydrogen peroxide can then be electrooxidized at the working electrode,which releases electrons to the working electrode, resulting in anamperometric current that can be measured through the working electrode.

The current generated by either reduction or oxidation reactions isapproximately proportionate to the reaction rate. Further, the reactionrate is dependent on the rate of analyte molecules reaching theelectrochemical sensor electrodes to fuel the reduction or oxidationreactions, either directly or catalytically through a reagent. In asteady state, where analyte molecules diffuse to the electrochemicalsensor electrodes from a sampled region at approximately the same ratethat additional analyte molecules diffuse to the sampled region fromsurrounding regions, the reaction rate is approximately proportionate tothe concentration of the analyte molecules. The current measured throughthe working electrode thus provides an indication of the analyteconcentration.

The controller 150 can optionally include a display driver module 154for operating a pixel array 164. The pixel array 164 can be an array ofseparately programmable light transmitting, light reflecting, and/orlight emitting pixels arranged in rows and columns. The individual pixelcircuits can optionally include liquid crystal technologies,microelectromechanical technologies, emissive diode technologies, etc.to selectively transmit, reflect, and/or emit light according toinformation from the display driver module 154. Such a pixel array 164can also optionally include more than one color of pixels (e.g., red,green, and blue pixels) to render visual content in color. The displaydriver module 154 can include, for example, one or more data linesproviding programming information to the separately programmed pixels inthe pixel array 164 and one or more addressing lines for setting groupsof pixels to receive such programming information. Such a pixel array164 situated on the eye can also include one or more lenses to directlight from the pixel array to a focal plane perceivable by the eye.

The controller 150 can also include a communication circuit 156 forsending and/or receiving information via the antenna 170. Thecommunication circuit 156 can optionally include one or moreoscillators, mixers, frequency injectors, etc. to modulate and/ordemodulate information on a carrier frequency to be transmitted and/orreceived by the antenna 170. In some examples, the eye-mountable device110 is configured to indicate an output from a bio-sensor by modulatingan impedance of the antenna 170 in a manner that is perceivably by theexternal reader 180. For example, the communication circuit 156 cancause variations in the amplitude, phase, and/or frequency ofbackscatter radiation from the antenna 170, and such variations can bedetected by the reader 180.

The controller 150 is connected to the bio-interactive electronics 160via interconnects 151. For example, where the controller 150 includeslogic elements implemented in an integrated circuit to form the sensorinterface module 152 and/or display driver module 154, a patternedconductive material (e.g., gold, platinum, palladium, titanium, copper,aluminum, silver, metals, combinations of these, etc.) can connect aterminal on the chip to the bio-interactive electronics 160. Similarly,the controller 150 is connected to the antenna 170 via interconnects157.

It is noted that the block diagram shown in FIG. 1 is described inconnection with functional modules for convenience in description.However, embodiments of the eye-mountable device 110 can be arrangedwith one or more of the functional modules (“sub-systems”) implementedin a single chip, integrated circuit, and/or physical feature. Forexample, while the rectifier/regulator 146 is illustrated in the powersupply block 140, the rectifier/regulator 146 can be implemented in achip that also includes the logic elements of the controller 150 and/orother features of the embedded electronics in the eye-mountable device110. Thus, the DC supply voltage 141 that is provided to the controller150 from the power supply 140 can be a supply voltage that is providedon a chip by rectifier and/or regulator components the same chip. Thatis, the functional blocks in FIG. 1 shown as the power supply block 140and controller block 150 need not be implemented as separated modules.Moreover, one or more of the functional modules described in FIG. 1 canbe implemented by separately packaged chips electrically connected toone another.

Additionally or alternatively, the energy harvesting antenna 142 and thecommunication antenna 170 can be implemented with the same physicalantenna. For example, a loop antenna can both harvest incident radiationfor power generation and communicate information via backscatterradiation.

The external reader 180 includes an antenna 188 (or group of more thanone antennae) to send and receive wireless signals 171 to and from theeye-mountable device 110. The external reader 180 also includes acomputing system with a processor 186 in communication with a memory182. The memory 182 is a non-transitory computer-readable medium thatcan include, without limitation, magnetic disks, optical disks, organicmemory, and/or any other volatile (e.g. RAM) or non-volatile (e.g. ROM)storage system readable by the processor 186. The memory 182 can includea data storage 183 to store indications of data, such as sensor readings(e.g., from the analyte bio-sensor 162), program settings (e.g., toadjust behavior of the eye-mountable device 110 and/or external reader180), etc. The memory 182 can also include program instructions 184 forexecution by the processor 186 to cause the external reader 180 toperform processes specified by the instructions 184. For example, theprogram instructions 184 can cause external reader 180 to provide a userinterface that allows for retrieving information communicated from theeye-mountable device 110 (e.g., sensor outputs from the analytebio-sensor 162). The external reader 180 can also include one or morehardware components for operating the antenna 188 to send and receivethe wireless signals 171 to and from the eye-mountable device 110. Forexample, oscillators, frequency injectors, encoders, decoders,amplifiers, filters, etc. can drive the antenna 188 according toinstructions from the processor 186.

The external reader 180 can be a smart phone, digital assistant, orother portable computing device with wireless connectivity sufficient toprovide the wireless communication link 171. The external reader 180 canalso be implemented as an antenna module that can be plugged in to aportable computing device, such as in an example where the communicationlink 171 operates at carrier frequencies not commonly employed inportable computing devices. In some instances, the external reader 180is a special-purpose device configured to be worn relatively near awearer's eye to allow the wireless communication link 171 to operatewith a low power budget. For example, the external reader 180 can beintegrated in a piece of jewelry such as a necklace, earing, etc. orintegrated in an article of clothing worn near the head, such as a hat,headband, etc.

In an example where the eye-mountable device 110 includes an analytebio-sensor 162, the system 100 can be operated to monitor the analyteconcentration in tear film on the surface of the eye. Thus, theeye-mountable device 110 can be configured as a platform for anophthalmic analyte bio-sensor. The tear film is an aqueous layersecreted from the lacrimal gland to coat the eye. The tear film is incontact with the blood supply through capillaries in the structure ofthe eye and includes many biomarkers found in blood that are analyzed tocharacterize a person's health condition(s). For example, the tear filmincludes glucose, calcium, sodium, cholesterol, potassium, otherbiomarkers, etc. The biomarker concentrations in the tear film can besystematically different than the corresponding concentrations of thebiomarkers in the blood, but a relationship between the twoconcentration levels can be established to map tear film biomarkerconcentration values to blood concentration levels. For example, thetear film concentration of glucose can be established (e.g., empiricallydetermined) to be approximately one tenth the corresponding bloodglucose concentration. Thus, measuring tear film analyte concentrationlevels provides a non-invasive technique for monitoring biomarker levelsin comparison to blood sampling techniques performed by lancing a volumeof blood to be analyzed outside a person's body. Moreover, theophthalmic analyte bio-sensor platform disclosed here can be operatedsubstantially continuously to enable real time monitoring of analyteconcentrations.

To perform a reading with the system 100 configured as a tear filmanalyte monitor, the external reader 180 can emit radio frequencyradiation 171 that is harvested to power the eye-mountable device 110via the power supply 140. Radio frequency electrical signals captured bythe energy harvesting antenna 142 (and/or the communication antenna 170)are rectified and/or regulated in the rectifier/regulator 146 and aregulated DC supply voltage 147 is provided to the controller 150. Theradio frequency radiation 171 thus turns on the electronic componentswithin the eye-mountable device 110. Once turned on, the controller 150operates the analyte bio-sensor 162 to measure an analyte concentrationlevel. For example, the sensor interface module 152 can apply a voltagebetween a working electrode and a reference electrode in the analytebio-sensor 162. The applied voltage can be sufficient to cause theanalyte to undergo an electrochemical reaction at the working electrodeand thereby generate an amperometric current that can be measuredthrough the working electrode. The measured amperometric current canprovide the sensor reading (“result”) indicative of the analyteconcentration. The controller 150 can operate the antenna 170 tocommunicate the sensor reading back to the external reader 180 (e.g.,via the communication circuit 156). The sensor reading can becommunicated by, for example, modulating an impedance of thecommunication antenna 170 such that the modulation in impedance isdetected by the external reader 180. The modulation in antenna impedancecan be detected by, for example, backscatter radiation from the antenna170.

In some embodiments, the system 100 can operate to non-continuously(“intermittently”) supply energy to the eye-mountable device 110 topower the controller 150 and electronics 160. For example, radiofrequency radiation 171 can be supplied to power the eye-mountabledevice 110 long enough to carry out a tear film analyte concentrationmeasurement and communicate the results. For example, the supplied radiofrequency radiation can provide sufficient power to apply a potentialbetween a working electrode and a reference electrode sufficient toinduce electrochemical reactions at the working electrode, measure theresulting amperometric current, and modulate the antenna impedance toadjust the backscatter radiation in a manner indicative of the measuredamperometric current. In such an example, the supplied radio frequencyradiation 171 can be considered an interrogation signal from theexternal reader 180 to the eye-mountable device 110 to request ameasurement. By periodically interrogating the eye-mountable device 110(e.g., by supplying radio frequency radiation 171 to temporarily turnthe device on) and storing the sensor results (e.g., via the datastorage 183), the external reader 180 can accumulate a set of analyteconcentration measurements over time without continuously powering theeye-mountable device 110.

FIG. 2A is a bottom view of an example eye-mountable electronic device210. FIG. 2B is an aspect view of the example eye-mountable electronicdevice shown in FIG. 2A. It is noted that relative dimensions in FIGS.2A and 2B are not necessarily to scale, but have been rendered forpurposes of explanation only in describing the arrangement of theexample eye-mountable electronic device 210. The eye-mountable device210 is formed of a polymeric material 220 shaped as a curved disk. Thepolymeric material 220 can be a substantially transparent material toallow incident light to be transmitted to the eye while theeye-mountable device 210 is mounted to the eye. The polymeric material220 can be a biocompatible material similar to those employed to formvision correction and/or cosmetic contact lenses in optometry, such aspolyethylene terephthalate (“PET”), polymethyl methacrylate (“PMMA”),silicone hydrogels, polyhydroxyethylmethacrylate (polyHEMA) basedhydrogels, and combinations of these, etc. The polymeric material 220can be formed with one side having a concave surface 226 suitable to fitover a corneal surface of an eye. The opposing side of the disk can havea convex surface 224 that does not interfere with eyelid motion whilethe eye-mountable device 210 is mounted to the eye. A circular outerside edge 228 connects the concave surface 224 and convex surface 226.

The eye-mountable device 210 can have dimensions similar to a visioncorrection and/or cosmetic contact lenses, such as a diameter ofapproximately 1 centimeter, and a thickness of about 0.1 to about 0.5millimeters. However, the diameter and thickness values are provided forexplanatory purposes only. In some embodiments, the dimensions of theeye-mountable device 210 can be selected according to the size and/orshape of the corneal surface of the wearer's eye.

The polymeric material 220 can be formed with a curved shape in avariety of ways. For example, techniques similar to those employed toform vision-correction contact lenses, such as heat molding, injectionmolding, spin casting, etc. can be employed to form the polymericmaterial 220. While the eye-mountable device 210 is mounted in an eye,the convex surface 224 faces outward to the ambient environment whilethe concave surface 226 faces inward, toward the corneal surface. Theconvex surface 224 can therefore be considered an outer, top surface ofthe eye-mountable device 210 whereas the concave surface 226 can beconsidered an inner, bottom surface. The “bottom” view shown in FIG. 2Ais facing the concave surface 226. From the bottom view shown in FIG.2A, the outer periphery 222, near the outer circumference of the curveddisk is curved out of the page, whereas the center region 221, near thecenter of the disk is curved in to the page.

A substrate 230 is embedded in the polymeric material 220. The substrate230 can be embedded to be situated along the outer periphery 222 of thepolymeric material 220, away from the center region 221. The substrate230 does not interfere with vision because it is too close to the eye tobe in focus and is positioned away from the center region 221 whereincident light is transmitted to the eye-sensing portions of the eye.Moreover, the substrate 230 can be formed of a transparent material tofurther mitigate any effects on visual perception.

The substrate 230 can be shaped as a flat, circular ring (e.g., a diskwith a central hole). The flat surface of the substrate 230 (e.g., alongthe radial width) is a platform for mounting electronics such as chips(e.g., via flip-chip mounting) and for patterning conductive materials(e.g., via deposition techniques) to form electrodes, antenna(e), and/orconnections. The substrate 230 and the polymeric material 220 can beapproximately cylindrically symmetric about a common central axis. Thesubstrate 230 can have, for example, a diameter of about 10 millimeters,a radial width of about 1 millimeter (e.g., an outer radius 1 millimetergreater than an inner radius), and a thickness of about 50 micrometers.However, these dimensions are provided for example purposes only, and inno way limit the present disclosure. The substrate 230 can beimplemented in a variety of different form factors.

A loop antenna 270, controller 250, and bio-interactive electronics 260are disposed on the embedded substrate 230. The controller 250 can be achip including logic elements configured to operate the bio-interactiveelectronics 260 and the loop antenna 270. The controller 250 iselectrically connected to the loop antenna 270 by interconnects 257 alsosituated on the substrate 230. Similarly, the controller 250 iselectrically connected to the bio-interactive electronics 260 by aninterconnect 251. The interconnects 251, 257, the loop antenna 270, andany conductive electrodes (e.g., for an electrochemical analytebio-sensor, etc.) can be formed from conductive materials patterned onthe substrate 230 by a process for precisely patterning such materials,such as deposition, lithography, etc. The conductive materials patternedon the substrate 230 can be, for example, gold, platinum, palladium,titanium, carbon, aluminum, copper, silver, silver-chloride, conductorsformed from noble materials, metals, combinations of these, etc.

As shown in FIG. 2A, which is a view facing the concave surface 226 ofthe eye-mountable device 210, the bio-interactive electronics module 260is mounted to a side of the substrate 230 facing the concave surface226. Where the bio-interactive electronics module 260 includes ananalyte bio-sensor, for example, mounting such a bio-sensor on thesubstrate 230 to be close to the concave surface 226 allows thebio-sensor to sense analyte concentrations in tear film near the surfaceof the eye. However, the electronics, electrodes, etc. situated on thesubstrate 230 can be mounted to either the “inward” facing side (e.g.,situated closest to the concave surface 226) or the “outward” facingside (e.g., situated closest to the convex surface 224). Moreover, insome embodiments, some electronic components can be mounted on one sideof the substrate 230, while other electronic components are mounted tothe opposing side, and connections between the two can be made throughconductive materials passing through the substrate 230.

The loop antenna 270 is a layer of conductive material patterned alongthe flat surface of the substrate to form a flat conductive ring. Insome instances, the loop antenna 270 can be formed without making acomplete loop. For instance, the loop antenna 270 can have a cutout toallow room for the controller 250 and bio-interactive electronics 260,as illustrated in FIG. 2A. However, the loop antenna 270 can also bearranged as a continuous strip of conductive material that wrapsentirely around the flat surface of the substrate 230 one or more times.For example, a strip of conductive material with multiple windings canbe patterned on the side of the substrate 230 opposite the controller250 and bio-interactive electronics 260. Interconnects between the endsof such a wound antenna (e.g., the antenna leads) can be passed throughthe substrate 230 to the controller 250.

FIG. 2C is a side cross-section view of the example eye-mountableelectronic device 210 while mounted to a corneal surface 22 of an eye10. FIG. 2D is a close-in side cross-section view enhanced to show thetear film layers 40, 42 surrounding the exposed surfaces 224, 226 of theexample eye-mountable device 210. It is noted that relative dimensionsin FIGS. 2C and 2D are not necessarily to scale, but have been renderedfor purposes of explanation only in describing the arrangement of theexample eye-mountable electronic device 210. For example, the totalthickness of the eye-mountable device can be about 200 micrometers,while the thickness of the tear film layers 40, 42 can each be about 10micrometers, although this ratio may not be reflected in the drawings.Some aspects are exaggerated to allow for illustration and facilitateexplanation.

The eye 10 includes a cornea 20 that is covered by bringing the uppereyelid 30 and lower eyelid 32 together over the top of the eye 10.Incident light is received by the eye 10 through the cornea 20, wherelight is optically directed to light sensing elements of the eye 10(e.g., rods and cones, etc.) to stimulate visual perception. The motionof the eyelids 30, 32 distributes a tear film across the exposed cornealsurface 22 of the eye 10. The tear film is an aqueous solution secretedby the lacrimal gland to protect and lubricate the eye 10. When theeye-mountable device 210 is mounted in the eye 10, the tear film coatsboth the concave and convex surfaces 224, 226 with an inner layer 40(along the concave surface 226) and an outer layer 42 (along the convexlayer 224). The tear film layers 40, 42 can be about 10 micrometers inthickness and together account for about 10 microliters.

The tear film layers 40, 42 are distributed across the corneal surface22 and/or the convex surface 224 by motion of the eyelids 30, 32. Forexample, the eyelids 30, 32 raise and lower, respectively, to spread asmall volume of tear film across the corneal surface 22 and/or theconvex surface 224 of the eye-mountable device 210. The tear film layer40 on the corneal surface 22 also facilitates mounting the eye-mountabledevice 210 by capillary forces between the concave surface 226 and thecorneal surface 22. In some embodiments, the eye-mountable device 210can also be held over the eye in part by vacuum forces against cornealsurface 22 due to the concave curvature of the eye-facing concavesurface 226.

As shown in the cross-sectional views in FIGS. 2C and 2D, the substrate230 can be inclined such that the flat mounting surfaces of thesubstrate 230 are approximately parallel to the adjacent portion of theconcave surface 226. As described above, the substrate 230 is aflattened ring with an inward-facing surface 232 (closer to the concavesurface 226 of the polymeric material 220) and an outward-facing surface234 (closer to the convex surface 224). The substrate 230 can haveelectronic components and/or patterned conductive materials mounted toeither or both mounting surfaces 232, 234. As shown in FIG. 2D, thebio-interactive electronics 260, controller 250, and conductiveinterconnect 251 are mounted on the inward-facing surface 232 such thatthe bio-interactive electronics 260 are relatively closer in proximityto the corneal surface 22 than if they were mounted on theoutward-facing surface 234. However, the bio-interactive electronics 260(and other components) can be mounted on the outward-facing surface 234of the substrate 230 to be closer to the outer tear film layer 42 thanthe inner tear film layer 40.

III. An Ophthalmic Electrochemical Analyte Sensor

FIG. 3 is a functional block diagram of a system 300 forelectrochemically measuring a tear film analyte concentration. Thesystem 300 includes an eye-mountable device 310 with embedded electroniccomponents powered by an external reader 340. The eye-mountable device310 includes an antenna 312 for capturing radio frequency radiation 341from the external reader 340. The eye-mountable device 310 includes arectifier 314, an energy storage 316, and regulator 318 for generatingpower supply voltages 330, 332 to operate the embedded electronics. Theeye-mountable device 310 includes an electrochemical sensor 320 with aworking electrode 322 and a reference electrode 323 driven by a sensorinterface 321. The eye-mountable device 310 includes hardware logic 324for communicating results from the sensor 320 to the external reader 340by modulating (325) the impedance of the antenna 312. Similar to theeye-mountable devices 110, 210 discussed above in connection with FIGS.1 and 2, the eye-mountable device 310 can include a mounting substrateembedded within a polymeric material configured to be mounted to an eye.The electrochemical sensor 320 can be situated on a mounting surface ofsuch a substrate proximate the surface of the eye (e.g., correspondingto the bio-interactive electronics 260 on the inward-facing side 232 ofthe substrate 230) to measure analyte concentration in a tear film layerinterposed between the eye-mountable device 310 and the eye (e.g., theinner tear film layer 40 between the eye-mountable device 210 and thecorneal surface 22).

With reference to FIG. 3, the electrochemical sensor 320 measuresanalyte concentration by applying a voltage between the electrodes 322,323 that is sufficient to cause products of the analyte catalyzed by thereagent to electrochemically react (e.g., a reduction and/or oxidizationreaction) at the working electrode 322. The electrochemical reactions atthe working electrode 322 generate an amperometric current that can bemeasured at the working electrode 322. The sensor interface 321 can, forexample, apply a reduction voltage between the working electrode 322 andthe reference electrode 323 to reduce products from thereagent-catalyzed analyte at the working electrode 322. Additionally oralternatively, the sensor interface 321 can apply an oxidation voltagebetween the working electrode 322 and the reference electrode 323 tooxidize the products from the reagent-catalyzed analyte at the workingelectrode 322. The sensor interface 321 measures the amperometriccurrent and provides an output to the hardware logic 324. The sensorinterface 321 can include, for example, a potentiostat connected to bothelectrodes 322, 323 to simultaneously apply a voltage between theworking electrode 322 and the reference electrode 323 and measure theresulting amperometric current through the working electrode 322.

The rectifier 314, energy storage 316, and voltage regulator 318 operateto harvest energy from received radio frequency radiation 341. The radiofrequency radiation 341 causes radio frequency electrical signals onleads of the antenna 312. The rectifier 314 is connected to the antennaleads and converts the radio frequency electrical signals to a DCvoltage. The energy storage 316 (e.g., capacitor) is connected acrossthe output of the rectifier 314 to filter high frequency noise on the DCvoltage. The regulator 318 receives the filtered DC voltage and outputsboth a digital supply voltage 330 to operate the hardware logic 324 andan analog supply voltage 332 to operate the electrochemical sensor 320.For example, the analog supply voltage can be a voltage used by thesensor interface 321 to apply a voltage between the sensor electrodes322, 323 to generate an amperometric current. The digital supply voltage330 can be a voltage suitable for driving digital logic circuitry, suchas approximately 1.2 volts, approximately 3 volts, etc. Reception of theradio frequency radiation 341 from the external reader 340 (or anothersource, such as ambient radiation, etc.) causes the supply voltages 330,332 to be supplied to the sensor 320 and hardware logic 324. Whilepowered, the sensor 320 and hardware logic 324 are configured togenerate and measure an amperometric current and communicate theresults.

The sensor results can be communicated back to the external reader 340via backscatter radiation 343 from the antenna 312. The hardware logic324 receives the output current from the electrochemical sensor 320 andmodulates (325) the impedance of the antenna 312 in accordance with theamperometric current measured by the sensor 320. The antenna impedanceand/or change in antenna impedance is detected by the external reader340 via the backscatter signal 343. The external reader 340 can includean antenna front end 342 and logic components 344 to decode theinformation indicated by the backscatter signal 343 and provide digitalinputs to a processing system 346. The external reader 340 associatesthe backscatter signal 343 with the sensor result (e.g., via theprocessing system 346 according to a pre-programmed relationshipassociating impedance of the antenna 312 with output from the sensor320). The processing system 346 can then store the indicated sensorresults (e.g., tear film analyte concentration values) in a local memoryand/or a network-connected memory.

In some embodiments, one or more of the features shown as separatefunctional blocks can be implemented (“packaged”) on a single chip. Forexample, the eye-mountable device 310 can be implemented with therectifier 314, energy storage 316, voltage regulator 318, sensorinterface 321, and the hardware logic 324 packaged together in a singlechip or controller module. Such a controller can have interconnects(“leads”) connected to the loop antenna 312 and the sensor electrodes322, 323. Such a controller operates to harvest energy received at theloop antenna 312, apply a voltage between the electrodes 322, 323sufficient to develop an amperometric current, measure the amperometriccurrent, and indicate the measured current via the antenna 312 (e.g.,through the backscatter radiation 343).

FIG. 4A is a flowchart of a process 400 for operating an amperometricsensor in an eye-mountable device to measure a tear film analyteconcentration. Radio frequency radiation is received at an antenna in aneye-mountable device including an embedded electrochemical sensor (402).Electrical signals due to the received radiation are rectified andregulated to power the electrochemical sensor and associated controller(404). For example, a rectifier and/or regulator can be connected to theantenna leads to output a DC supply voltage for powering theelectrochemical sensor and/or controller. A voltage sufficient to causeelectrochemical reactions at the working electrode is applied between aworking electrode and a reference electrode on the electrochemicalsensor (406). An amperometric current is measured through the workingelectrode (408). For example, a potentiostat can apply a voltage betweenthe working and reference electrodes while measuring the resultingamperometric current through the working electrode. The measuredamperometric current is wirelessly indicated with the antenna (410). Forexample, backscatter radiation can be manipulated to indicate the sensorresult by modulating the antenna impedance.

FIG. 4B is a flowchart of a process 420 for operating an external readerto interrogate an amperometric sensor in an eye-mountable device tomeasure a tear film analyte concentration. Radio frequency radiation istransmitted to an electrochemical sensor mounted in an eye from theexternal reader (422). The transmitted radiation is sufficient to powerthe electrochemical sensor with energy from the radiation for longenough to perform a measurement and communicate the results (422). Forexample, the radio frequency radiation used to power the electrochemicalsensor can be similar to the radiation 341 transmitted from the externalreader 340 to the eye-mountable device 310 described in connection withFIG. 3 above. The external reader then receives backscatter radiationindicating the measurement by the electrochemical analyte sensor (424).For example, the backscatter radiation can be similar to the backscattersignals 343 sent from the eye-mountable device 310 to the externalreader 340 described in connection with FIG. 3 above. The backscatterradiation received at the external reader is then associated with a tearfilm analyte concentration (426). In some cases, the analyteconcentration values can be stored in the external reader memory (e.g.,in the processing system 346) and/or a network-connected data storage.

For example, the sensor result (e.g., the measured amperometric current)can be encoded in the backscatter radiation by modulating the impedanceof the backscattering antenna. The external reader can detect theantenna impedance and/or change in antenna impedance based on afrequency, amplitude, and/or phase shift in the backscatter radiation.The sensor result can then be extracted by associating the impedancevalue with the sensor result by reversing the encoding routine employedwithin the eye-mountable device. Thus, the reader can map a detectedantenna impedance value to an amperometric current value. Theamperometric current value is approximately proportionate to the tearfilm analyte concentration with a sensitivity (e.g., scaling factor)relating the amperometric current and the associated tear film analyteconcentration. The sensitivity value can be determined in part accordingto empirically derived calibration factors, for example.

IV. Analyte Transmission to the Electrochemical Sensor

FIG. 5A shows an example configuration in which an electrochemicalsensor detects an analyte from the inner tear film layer 40 thatdiffuses through the polymeric material 220. The electrochemical sensorcan be similar to the electrochemical sensor 320 discussed in connectionwith FIG. 3 and includes a working electrode 520 and a referenceelectrode 522. The working electrode 520 and the reference electrode 522are each mounted on an inward-facing side of the substrate 230. Thesubstrate 230 is embedded in the polymeric material 220 of theeye-mountable device 210 such that the electrodes 520, 522 of theelectrochemical sensor are entirely covered by an overlapping portion512 of the polymeric material 220. The electrodes 520, 522 in theelectrochemical sensor are thus separated from the inner tear film layer40 by the thickness of the overlapping portion 512. The thickness of theoverlapping region 512 can be approximately 10 micrometers, for example.

An analyte in the tear film diffuses through the overlapping portion 512to the working electrode 520. The diffusion of the analyte from theinner tear film layer 40 to the working electrode 520 is illustrated bythe directional arrow 510. The current measured through the workingelectrode 520 is based on the electrochemical reaction rate at theworking electrode 520, which in turn is based on the amount of analytediffusing to the working electrode 520. The amount of analyte diffusingto the working electrode 520 can in turn be influenced both by theconcentration of analyte in the inner tear film layer 40, thepermeability of the polymeric material 220 to the analyte, and thethickness of the overlapping region 512 (i.e., the thickness ofpolymeric material the analyte diffuses through to reach the workingelectrode 520 from the inner tear film layer 40). In the steady stateapproximation, the analyte is resupplied to the inner tear film layer 40by surrounding regions of the tear film 40 at the same rate that theanalyte is consumed at the working electrode 520. Because the rate atwhich the analyte is resupplied to the probed region of the inner tearfilm layer 40 is approximately proportionate to the tear filmconcentration of the analyte, the current (i.e., the electrochemicalreaction rate) is an indication of the concentration of the analyte inthe inner tear film layer 40.

Where the polymeric material is relatively impermeable to the analyte ofinterest, less analyte reaches the electrodes 520, 522 from the innertear film layer 40 and the measured amperometric current is thereforesystematically lower, and vice versa. The systematic effects on themeasured amperometric currents can be accounted for by a scaling factorin relating measured amperometric currents to tear film concentrations.Although after the eye-mountable device is in place over the eye for aperiod of time, the analyte concentration itself can be influenced bythe permeability of the polymeric material 220 if the analyte is onewhich is supplied to the tear film by the atmosphere, such as molecularoxygen. For example, if the polymeric material 220 is completelyimpermeable to molecular oxygen, the molecular oxygen concentration ofthe inner tear film layer 40 can gradually decrease over time while theeye is covered, such as by an exponential decay with a half life givenapproximately by the time for half of the oxygen molecules in the innertear film layer 40 to diffuse into the corneal tissue. On the otherhand, where the polymeric material 220 is completely oxygen permeable,the molecular oxygen concentration of the inner tear film layer 40 canbe largely unaffected over time, because molecular oxygen that diffusesinto the corneal tissue is replaced by molecular oxygen that permeatesthrough the polymeric material 220 from the atmosphere.

FIG. 5B shows an example configuration in which an electrochemicalsensor detects an analyte from the tear film that contacts the sensorvia a channel 530 in the polymeric material 220. The channel 530 hasside walls 532 that connect the concave surface 226 of the polymericmaterial 220 to the substrate 230 and/or electrodes 520, 522. Thechannel 530 can be formed by pressure molding or casting the polymericmaterial 220 for example. The height of the channel 530 (e.g., thelength of the sidewalls 532) corresponds to the separation between theinward-facing surface of the substrate 230 and the concave surface 226.That is, where the substrate 230 is positioned about 10 micrometers fromthe concave surface 226, the channel 530 is approximately 10 micrometersin height. The channel 530 fluidly connects the inner tear film layer 40to the sensor electrodes 520, 522. Thus, the working electrode 520 is indirect contact with the inner tear film layer 40. As a result, analytetransmission to the working electrode 520 is unaffected by thepermeability of the polymeric material 220 to the analyte of interest.The indentation 542 in the concave surface 226 also creates a localizedincreased volume of the tear film 40 near the sensor electrodes 520,522. The volume of analyte tear film that contributes analytes to theelectrochemical reaction at the working electrode 520 (e.g., bydiffusion) is thereby increased. The sensor shown in FIG. 5B istherefore less susceptible to a diffusion-limited electrochemicalreaction, because a relatively greater local volume of tear filmsurrounds the sampled region to contribute analytes to theelectrochemical reaction.

FIG. 5C shows an example configuration in which an electrochemicalsensor detects an analyte from the tear film 40 that diffuses through athinned region 542 of the polymeric material 220. The thinned region 542can be formed as an indentation 540 in the concave surface 226 (e.g., bymolding, casting, etc.). The thinned region 542 of the polymericmaterial 220 substantially encapsulates the electrodes 520, 522, so asto maintain a biocompatible coating between the cornea 20 and theworking electrodes 520, 522. The indentation 542 in the concave surface226 also creates a localized increased volume of the tear film 40 nearthe sensor electrodes 520, 522. A directional arrow 544 illustrates thediffusion of the analyte from the inner tear film layer 40 to theworking electrode 520.

FIG. 5D shows an example configuration in which an electrochemicalsensor detects an analyte that diffuses from an outer tear film 42 layerthrough a polymeric material 220. The working electrode 520 and thereference electrode 522 are each mounted on an outward-facing side ofthe substrate 230 (e.g., the outward-facing surface 234 discussed inconnection with FIG. 2 above). The electrodes 520, 522 of theelectrochemical sensor are entirely covered by an overlapping portion554 of the polymeric material 220. The electrodes 520, 522 in theelectrochemical sensor are thus separated from the outer tear film layer42 by the thickness of the overlapping portion 554. The thickness of theoverlapping region 554 can be approximately 10 micrometers, for example.An analyte in the outer tear film layer 42 diffuses through theoverlapping portion 554 to the working electrode 520. The diffusion ofthe analyte from the outer tear film layer 42 to the working electrode520 is illustrated by the directional arrow 560.

FIG. 5E shows an example configuration in which an electrochemicalsensor detects an analyte in an outer tear film layer 42 that contactsthe sensor via a channel 562 in a polymeric material 220. The channel562 connects the convex surface 224 of the polymeric material 220 to thesubstrate 230 and/or electrodes 520, 522. The channel 562 can be formedby pressure molding or casting the polymeric material 220 for example.The height of the channel 562 corresponds to the separation between theoutward-facing surface of the substrate 230 (e.g., the outward-facingsurface 234 discussed in connection with FIG. 2 above) and the convexsurface 224. That is, where the substrate 230 is positioned about 10micrometers from the convex 224, the channel 562 is approximately 10micrometers in height. The channel 562 fluidly connects the outer tearfilm layer 42 to the sensor electrodes 520, 522. Thus, the workingelectrode 520 is in direct contact with the outer tear film layer 42. Asa result, analyte transmission to the working electrode 520 isunaffected by the permeability of the polymeric material 220 to theanalyte of interest. The channel 562 in the convex surface 224 alsocreates a localized increased volume of the tear film 42 near the sensorelectrodes 520, 522. The volume of analyte tear film that contributesanalytes to the electrochemical reaction at the working electrode 520(e.g., by diffusion) is thereby increased. The sensor shown in FIG. 5Eis therefore less susceptible to a diffusion-limited electrochemicalreaction, because a relatively greater local volume of tear filmsurrounds the sampled region to contribute analytes to theelectrochemical reaction.

FIG. 5F shows an example configuration in which an electrochemicalsensor detects an analyte that diffuses from an outer tear film layer 42through a thinned region of a polymeric material 220. The thinned region556 can be formed as an indentation 564 in the convex surface 224 (e.g.,by molding, casting, etc.). The thinned region 556 of the polymericmaterial 220 substantially encapsulates the electrodes 520, 522. Theindentation 564 in the convex surface 224 also creates a localizedincreased volume of the tear film 42 near the sensor electrodes 520,522. A directional arrow 566 illustrates the diffusion of the analytefrom the outer tear film layer 42 to the working electrode 520.

FIGS. 5A through 5C illustrate arrangements in which an electrochemicalsensor is mounted on a surface of the substrate 230 proximate theconcave surface 226 (e.g., the inward-facing surface 232 discussed inconnection with FIG. 2 above). An electrochemical sensor arranged asshown in FIGS. 5A through 5C is thus configured to detect an analyteconcentration of the inner tear film layer 40, which diffuses into thepolymeric material 220 from the concave surface 226. FIGS. 5D through 5Fillustrate arrangements in which an electrochemical sensor is mounted ona surface of the substrate 230 proximate the convex surface 224 (e.g.,the outward-facing surface 234 discussed in connection with FIG. 2above). An electrochemical sensor arranged as shown in FIGS. 5D through5F is thus configured to detect an analyte concentration of the outertear film layer 42, which diffuses into the polymeric material 220 fromthe convex surface 224. By situating the electrochemical sensor on theoutward-facing surface of the substrate 230, as shown in FIGS. 5Dthrough 5F, for example, the electrodes 520, 522 are separated from thecornea 20 of the eye 10 by the substrate 230. The substrate 230 can thusshield the cornea 20 from damage associated with direct exposure to theelectrodes 520, 522, such as may occur due to puncturing or wearingthrough the polymeric material 220, for example.

V. Example Microelectrode Arrangements

FIG. 6A illustrates one example arrangement for electrodes in anelectrochemical sensor 601. The arrangement illustrated by FIG. 6A isnot drawn to scale, but instead is provided for explanatory purposes todescribe an example arrangement. The electrochemical sensor 601 can beincluded in an eye-mountable device for detecting a tear filmconcentration of an analyte (e.g., the eye-mountable devices describedin connection with FIGS. 1-3 above). The electrochemical sensor includesa working electrode 620 and a reference electrode 622 arranged asconductive bars disposed on a substrate. The conductive bars can bearranged in parallel such that the separation between the electrodes620, 622 is substantially uniform along the respective lengths of theelectrodes 620, 622. In some embodiments, at least one of the dimensionsof the working electrode 620, such as its width, can be less than 100micrometers. In some embodiments, the working electrode 620 is amicroelectrode with at least one dimension of about 25 micrometers. Insome embodiments, the working electrode 620 is a microelectrode with atleast one dimension of about 10 micrometers. In some embodiments, theworking electrode 620 is a microelectrode with at least one dimensionless than 10 micrometers. The thickness (e.g., height on the substrate)can be 1 micrometer or less. The thickness dimension can be, forexample, between about 1 micrometer and about 50 nanometer, such asapproximately 500 nanometers, approximately 250 nanometers,approximately 100 nanometers, approximately 50 nanometers, etc. Forexample, the bar-shaped working electrode 620 can be a conductivematerial patterned on a substrate to have a width of about 25micrometers, a length of about 1000 micrometers, and a thickness ofabout 0.5 micrometers. In some embodiments, the reference electrode 622can be larger in area (e.g., length multiplied by width) than theworking electrode 620. For example, the reference electrode 622 have anarea more than five times greater than the area of the working electrode620.

The electrodes 620, 622 can each be formed by patterning conductivematerials on a substrate (e.g., by deposition techniques, lithographytechniques, etc.). The conductive materials can be gold, platinum,palladium, titanium, silver, silver-chloride, aluminum, carbon, metals,conductors formed from noble materials, combinations of these, etc. Insome embodiments, the working electrode 620 can be formed substantiallyfrom platinum (Pt). In some embodiments, the reference electrode 622 canbe formed substantially from silver silver-chloride (Ag/AgCl).

The electrodes 620, 622 are each electrically connected to apotentiostat 610 which operates the sensor 601 by applying a voltagedifference ΔV between the working electrode 620 and the referenceelectrode 622. The voltage difference ΔV can be a reduction voltagesufficient to cause a reduction reaction at the working electrode 620that releases electrons from the working electrode 620 and therebygenerates an amperometric current that can be measured through theworking electrode 620. Additionally or alternatively, the voltagedifference ΔV can be an oxidization voltage sufficient to cause anoxidization reaction at the working electrode 620 that contributeselectrons to the working electrode 620 and thereby generates anamperometric current that can be measured through the working electrode620. The potentiostat 610 is powered by a supply voltage Vsupply andoutputs an indication of the amperometric current.

FIG. 6B illustrates another example arrangement for electrodes in anelectrochemical sensor 602. The arrangement illustrated by FIG. 6B isnot drawn to scale, but instead is provided for explanatory purposes todescribe the example arrangement. The electrochemical sensor 602 can beincluded in an eye-mountable device for detecting tear film oxygenconcentrations and/or other analytes (e.g., the eye-mountable devicesdescribed in connection with FIGS. 1-3 above). The electrochemicalsensor includes a working electrode 630 and a reference electrode 632arranged as flattened rings situated on a substrate. The flattened ringscan be arranged concentrically (e.g., with a common center point) suchthat the separation between the electrodes 630, 632 is substantiallyuniform along the circumferential edges of the respective electrodes630, 632. The reference electrode 632 is illustrated as an outer ring,with the working electrode 630 as an inner ring, but this inner/outerrelationship can be reversed in some implementations. In someembodiments, at least one of the dimensions of the working electrode630, such as its radial width, can be less than 100 micrometers. In someembodiments, the working electrode 630 is a microelectrode with at leastone dimension of about 25 micrometers. In some embodiments, the workingelectrode 630 is a microelectrode with at least one dimension of about10 micrometers. In some embodiments, the working electrode 630 is amicroelectrode with at least one dimension less than 10 micrometers. Thethickness (e.g., height on the substrate) can be 1 micrometer or less.For example, the flattened-ring-shaped working electrode 630 can be aconductive material patterned on a substrate to have a circumference ofabout 1000 micrometers, a radial width of about 25 micrometers, and athickness of about 0.5 micrometers.

The electrodes 630, 632 can be formed by the materials and patterningtechniques described above in connection with the electrodes 620, 622 inFIG. 6A. The electrodes 630, 632 can also be operated by thepotentiostat 610 to measure an amperometric current similarly to thediscussion of the potentiostat 610 above in connection with FIG. 6A.

FIG. 7A illustrates an example coplanar arrangement for electrodes in atwo-electrode electrochemical sensor. In this configuration, the twoelectrodes, a working electrode 720 and a reference electrode 722, aremounted on a substrate 730 that is covered by a layer of polymericmaterial 710. In FIG. 7A, the portion 711 of the polymeric material 710that covers electrodes 720 and 720 is indicated by dashed lines in orderto show electrodes 720 and 722. Thus, in this example, the two-electrodeelectrochemical sensor includes a working electrode 720 and a referenceelectrode 722 that are mounted on the same surface of substrate 730, andpolymeric material 710 forms a layer encapsulating both the workingelectrode 720 and the reference electrode 722. For example, thesubstrate 730 can be shaped as a flattened ring suitable for beingmounted within an eye-mountable polymeric material, similar to thesubstrates described above in connection with FIGS. 1-5. The polymericmaterial 710 can have an exposed surface 714 that is suitable forcontact mounting to an eye, similar to the concave surface 226 of theeye-mountable device 210 discussed above in connection with FIG. 2. Theexposed surface 714 can also be suitable for avoiding interference witheyelid motion while an opposing surface of the polymeric material iscontact mounted to an eye, similar to the convex surface 224 of theeye-mountable device 210 discussed above in connection with FIG. 2.Thus, the electrodes 720, 722 can be mounted to an eye-facing surfaceand/or an outward facing surface of the substrate 730.

The electrodes 720, 722 can each be formed by patterning conductivematerials on a substrate (e.g., by deposition techniques, lithographytechniques, etc.). The conductive materials can be gold, platinum,palladium, titanium, silver, silver-chloride, aluminum, carbon, metals,conductors formed from noble materials, combinations of these, etc.

As shown in FIG. 7A, the working electrode 720 has a width w1 and thereference electrode has a width w2. The width w1 of the workingelectrode 720 can be, for example, less than 25 micrometers. In someembodiments, the width w1 can be about 10 micrometers. In someembodiments, the width w1 can be less than 10 micrometers. The width w2can be selected such that the area of the reference electrode 722 (e.g.,width w2 multiplied by length) is at least five times greater than thearea of the working electrode 720 (e.g., width w1 multiplied by length).The lengths of the two electrodes 720, 722 can be approximately equaland can be, for example, 1 millimeter. The height (“thickness”) of theelectrodes 720, 722 can be, for example, about 0.5 micrometers. Wherethe lengths of the two electrodes 720, 722 are approximately equal, theratio between electrode areas is given by the ratio of the widths w1 andw2. Thus, in some embodiments, the width w2 of the reference electrode722 is at least five times greater than the width w1 of the workingelectrode 720.

The distance d1 between the electrodes 720, 722 can be substantiallyconstant along the length of the electrodes 720, 722 (e.g., parts of theelectrodes 720, 722 can be oriented as parallel bars and/or asconcentric rings such that the distance d1 separating them isapproximately constant). In some embodiments, the distance d1 is betweenabout 10 micrometers and about 500 micrometers.

By situating the working electrode 720 and the reference electrode 722on the same surface of the substrate 730, the electrodes 720, 722 can bearranged to be approximately coplanar, and the distance d1 separatingthe two electrodes 720, 722 can be measured substantially within a planeof the two electrodes.

The polymeric material 710 includes an interposed portion 712 that issituated between the two electrodes 720, 722. In this configuration,electrical current that is conveyed between the electrodes 720, 722 ispassed through the interposed portion 712 of polymeric material 710. Forexample, such a current can be conveyed ionically (e.g., by electrolytesfrom the tear film that are absorbed in the polymeric material 710)while an amperometric current is generated by electrochemical reactionsat the working electrode 720. The interposed portion 712 thus provides acurrent carrying medium between the electrodes 720, 722 that isanalogous to an electrolyte-containing fluid medium. However, theinterposed portion 712 of the polymeric material 710 can have a greaterelectrical resistance than a typical electrolyte-containing fluidmedium. Because of the relatively high electrical resistance of theinterposed portion 712, the current conveyed between the electrodesresults in a voltage drop across interposed portion 712.

However, by configuring working electrode 720 with sufficiently smalldimensions (e.g., with a width w1 less than 25 micrometers), the currentconveyed between electrodes 720 and 722 can be sufficiently small suchthat the voltage drop caused by the resistance of interposed portion 712of the polymeric material 710 is inconsequential to the operation of theelectrochemical sensor.

While such a current is conveyed between the two electrodes, the currentdensity through the two electrodes 720, 722 is inversely proportional tothe area of the respective electrodes 720, 722. As a result, thereference electrode 722 experiences a smaller current density than theworking electrode 720 (e.g., at least five times less). The smallercurrent density allows the voltage on the reference electrode 722 to berelatively less affected by the conveyed current and thereby facilitatesthe operation of a potentiostat (or other control module) to apply astable voltage difference between the electrodes 720, 722 whilemeasuring the amperometric current through the working electrode.

A reagent layer 724 can be localized proximate the working electrode720. The reagent layer 724 can sensitize the two-electrodeelectrochemical sensor to an analyte of interest For example, glucoseoxidase can be employed to detect glucose by catalyzing glucoseoxidation to generate hydrogen peroxide, which is then oxidized at theworking electrode 720. The reagent layer 724 can be fixed to wholly orpartially surround the working electrode 720, for example. In someembodiments, the reagent layer 724 can be fixed proximate only theworking electrode 720, and not the reference electrode 722. In someembodiments, a reagent layer can be overlaid to cover both electrodes720, 722.

FIG. 7B illustrates an example non-coplanar arrangement for electrodesin a two-electrode electrochemical sensor. In particular, FIG. 7B showsa perspective cross-sectional view of electrodes mounted on a substrate760 that is covered by a layer polymeric material 740. Thus, thetwo-electrode electrochemical sensor includes a working electrode 750and a reference electrode 752, and the polymeric material 740 includes aportion 741 (indicated by dashed lines) that covers the electrodes 750,752. In some examples, polymeric material 740 has an exposed surface 742that can be a surface configured to contact mounted to a corneal surfaceof an eye, similar to the concave surface 226 of the eye-mountabledevice 210 discussed above in connection with FIG. 2. The exposedsurface 742 can also be suitable for avoiding interference with eyelidmotion while an opposing surface of the polymeric material is contactmounted to an eye, similar to the convex surface 224 of theeye-mountable device 210 discussed above in connection with FIG. 2.Thus, the electrodes 750, 752 can be mounted to an eye-facing surfaceand/or an outward facing surface of the substrate 760.

The substrate 760 can be shaped as a flattened ring suitable for beingmounted within an eye-mountable polymeric material, similar to thesubstrates described above. The reference electrode 752 and the workingelectrode 750 are mounted to the substrate 740 to be non-coplanar. Thatis, the electrodes 750, 752 can be mounted with the working electrode750 stacked over the reference electrode 752 such that the workingelectrode 750 is a greater distance from the exposed surface 742 of thepolymeric material 740 than the working electrode 750. As a result,where the exposed surface 742 is mounted over an eye, the workingelectrode 750 is closer to the surface of the eye than the referenceelectrode 752 by the distance d2 separating the two electrodes 750, 752.The separation distance d2 between the two electrodes 750, 752 istherefore measured transverse to the planes of the two electrodes.

The dimensions of the working electrode 750 and the reference electrode752, respectively can be similar to the dimensions of the workingelectrode 720 and the reference electrode 722 described above inconnection with FIG. 7A. For example, the area of the referenceelectrode 752 can be at least five times greater than the area of theworking electrode 750.

Current between the electrodes 750, 752 can be conveyed through aninterposed portion 762 of the polymeric material 740. Electrical currentcan be carried ionically between the electrodes 750, 752 throughinterposed portion 762 in a manner similar to the interposed portion 712described in connection with FIG. 7A above.

A reagent layer 754 can be localized proximate the working electrode750. The reagent layer 754 can sensitize the two-electrodeelectrochemical sensor to an analyte of interest For example, glucoseoxidase can be employed to detect glucose by catalyzing glucoseoxidation to generate hydrogen peroxide, which is then oxidized at theworking electrode 750. The reagent layer 754 can be fixed to wholly orpartially surround the working electrode 750, for example. In someembodiments, the reagent layer 754 can be fixed proximate only theworking electrode 750, without being proximate the reference electrode752. In some embodiments, a reagent layer can be overlaid to cover bothelectrodes 750, 752.

The electrode arrangements described in connection with FIGS. 6A, 6B,7A, and 7B above can be employed in any of the electrochemical sensorsdescribed herein. Moreover, some embodiments of the present disclosurecan include electrode arrangements that combine aspects from theparallel bar arrangement discussed in connection with FIG. 6A and fromthe concentric ring arrangement discussed in connection with FIG. 6B.Additionally or alternatively, some embodiments of the presentdisclosure can include electrode arrangements that combine aspects fromthe coplanar arrangement discussed in connection with FIG. 7A and fromthe non-coplanar arrangement discussed in connection with FIG. 7B. Forexample, the electrodes 520, 522 of the electrochemical analyte sensordescribed in connection with FIG. 5 can be arranged as non-coplanarflattened rings (as described in connection with FIGS. 6A and 7B, forexample) or as approximately coplanar parallel bars (as described inconnection with FIGS. 6B and 7A, for example). Similarly, theelectrochemical sensors 260 and 320 described in connection with FIGS. 2and 3 can be implemented with sensor electrodes arranged similarly tothe electrodes 620, 622 in FIG. 6A, the electrodes 630, 632 in FIG. 6B,the electrodes 720, 722 in FIG. 7A, and/or the electrodes 750, 752 inFIG. 7B.

When the dimensions of the working electrode in any of theconfigurations described herein are made sufficiently small (e.g., awidth of less than 25 micrometers, about 10 micrometers, or less than 10micrometers) the current passing through the working electrode can be inthe nA range. At such low currents, the diffusion layer thicknessinduced at these electrodes is very small (on the order of a fewmicrometers). As a result, the diffusion of analytes to the electrode isextremely efficient and a steady state current can be obtained. In someembodiments, the induced consumption (electrolysis) of analytes is alsodecreased and a continuous mode of operation of the sensor can berealized. The relatively small diffusion layer associated with asmall-dimensioned working electrode can also reduce adverse effectsassociated with the mass transfer of analytes to the electrode surface,such as noise caused by irregular mass transfer of analytes.

By configuring the working electrode with sufficiently small dimensions(e.g., a width of less than 25 micrometers, about 10 micrometers, orless than 10 micrometers), the charging current resulting from thecapacitive effects of the electrode-electrolyte interface canbeneficially be reduced. This is because the capacitive current isproportional to the electrode area.

In general, configuring a working electrode as a microelectrode with adimension less than 25 micrometers (or less than 10 micrometers) canprovide various advantages over larger-dimensioned electrodes. Moreover,the smaller currents associated with microelectrode-sized workingelectrodes makes them particularly well suited for their use in a mediumwith high resistance, such as the polymeric materials that may be usedin the eye-mountable devices described herein.

While various aspects and embodiments have been disclosed herein, otheraspects and embodiments will be apparent to those skilled in the art.The various aspects and embodiments disclosed herein are for purposes ofillustration and are not intended to be limiting, with the true scopebeing indicated by the following claims.

What is claimed is:
 1. An eye-mountable device, comprising: a transparent polymeric material having a concave surface and a convex surface, wherein the concave surface is configured to be removably mounted over a corneal surface and the convex surface is configured to be compatible with eyelid motion when the concave surface is so mounted, and wherein the transparent polymeric material includes channel in the convex surface; a substrate at least partially embedded within the polymeric material; an antenna disposed on the substrate; a two-electrode electrochemical sensor disposed on a surface of the substrate and including: a working electrode having a width dimension equal to or less than 25 micrometers, wherein the width dimension is substantially parallel to the surface of the substrate; and a reference electrode having an area at least five times greater than an area of the working electrode; and a controller electrically connected to the electrochemical sensor and the antenna, wherein the controller is configured to: (i) apply a voltage between the working electrode and the reference electrode sufficient to generate an amperometric current related to the concentration of an analyte in a fluid to which the eye-mountable device is exposed; (ii) measure the amperometric current; and (iii) use the antenna to indicate the measured amperometric current, wherein the working electrode and the reference electrode are both exposed by the channel to provide direct contact with the fluid.
 2. The eye-mountable device according to claim 1, wherein the channel is configured to fluidly connect an outer tear film layer to the working electrode and reference electrode while the transparent polymeric material is mounted over the corneal surface.
 3. The eye-mountable device according to claim 1, wherein the width dimension of the working electrode is approximately equal to 10 micrometers.
 4. The eye-mountable device according to claim 1, wherein the width dimension of the working electrode is less than 10 micrometers.
 5. The eye-mountable device according to claim 1, wherein the working electrode and the reference electrode are each disposed on the substrate so as to be approximately coplanar.
 6. The eye-mountable device according to claim 1, further comprising a reagent that selectively reacts with the analyte, wherein the reagent is localized proximate the working electrode.
 7. The eye-mountable device according to claim 6, wherein the reagent is localized away from the reference electrode.
 8. The eye-mountable device according to claim 1, further comprising a power supply disposed on the substrate and electrically connected to the antenna and the controller, wherein the power supply is configured to convert power from radio frequency radiation received by the antenna into electrical power and to supply the electrical power to the controller.
 9. The eye-mountable device according to claim 1, wherein the controller is configured to indicate the measured amperometric current by modulating an impedance of the antenna.
 10. The eye-mountable device according to claim 1, wherein the electrochemical sensor is situated on a mounting surface of the substrate proximate the convex surface of the polymeric material.
 11. The eye-mountable device according to claim 1, wherein the polymeric material is a substantially transparent vision correction lens and is shaped to provide a predetermined vision-correcting optical power.
 12. A system comprising: an eye-mountable device including: a transparent polymeric material having a concave surface and a convex surface, wherein the concave surface is configured to be removably mounted over a corneal surface and the convex surface is configured to be compatible with eyelid motion when the concave surface is so mounted, and wherein the transparent polymeric material includes a channel in the convex surface; a substrate at least partially embedded within the polymeric material; an antenna disposed on the substrate; a two-electrode electrochemical sensor disposed on a surface of the substrate and including: a working electrode having a width dimension equal to or less than 25 micrometers, wherein the width dimension is substantially parallel to the surface of the substrate; and a reference electrode having an area at least five times greater than an area of the working electrode; and a controller electrically connected to the electrochemical sensor and the antenna, wherein the controller is configured to: (i) apply a voltage between the working electrode and the reference electrode sufficient to generate an amperometric current related to the concentration of an analyte in a fluid to which the eye-mountable device is exposed; (ii) measure the amperometric current; and (iii) use the antenna to indicate the measured amperometric current, wherein the working electrode and the reference electrode are both exposed by the channel to provide direct contact with the fluid such that operation of the two-electrode electrochemical sensor is substantially unaffected by a permeability of the transparent polymeric material to the analyte; and a reader including: one or more antennae configured to: transmit radio frequency radiation to power the eye-mountable device, and receive indications of the measured amperometric current via backscatter radiation received at the one or more antennae; and a processing system configured to determine a tear film analyte concentration value based on the backscatter radiation.
 13. The system according to claim 12, wherein the channel is configured to fluidly connect an outer tear film layer to the working electrode and reference electrode while the transparent polymeric material is mounted over the corneal surface.
 14. The system according to claim 12, wherein the width dimension of the working electrode is approximately equal to 10 micrometers.
 15. The system according to claim 12, wherein the width dimension of the working electrode is a microelectrode having at least one dimension less than 10 micrometers.
 16. The system according to claim 12, wherein the working electrode and the reference electrode are each disposed on the substrate so as to be approximately coplanar.
 17. The system according to claim 12, further comprising a reagent that selectively reacts with the analyte, wherein the reagent is localized proximate the working electrode.
 18. The system according to claim 12, wherein the eye-mountable device further includes a power supply disposed on the substrate and electrically connected to the antenna and the controller, wherein the power supply is configured to convert power from radio frequency radiation received by the antenna into electrical power and to supply the electrical power to the controller, wherein the controller is configured to indicate the measured amperometric current by adjusting an impedance of the antenna included in the eye-mountable device, and wherein the reader is configured to wirelessly sense the impedance of the antenna.
 19. A method comprising: applying a voltage between a working electrode and a reference electrode sufficient to cause electrochemical reactions at the working electrode, wherein the working electrode and the reference electrode are disposed on a surface of a substrate embedded within an eye-mountable device that includes a transparent polymeric material having a concave surface and a convex surface, wherein the concave surface is configured to be removably mounted over a corneal surface and the convex surface is configured to be compatible with eyelid motion when the concave surface is so mounted, and wherein the transparent polymeric material includes a channel in the convex surface, wherein the working electrode has a width dimension equal to or less than 25 micrometers, wherein the width dimension is substantially parallel to the surface of the substrate, wherein the reference electrode has an area at least five times greater than an area of the working electrode, and wherein the working electrode and the reference electrode are both exposed by the channel to a fluid such that the electrochemical reactions are related to a concentration of an analyte in the fluid, wherein the fluid enters the channel and forms direct contact with both of the working and reference electrodes; while applying the voltage, measuring an amperometric current through the working electrode; and wirelessly indicating the measured amperometric current via an antenna embedded within the eye-mountable device.
 20. The method according to claim 19, wherein the width dimension of the working electrode is less than or approximately equal to 10 micrometers. 